Full Grants

• Prof. Daniel Offen | Dept. Human Molecular Genetics and Biochemistry, Gray Faculty of Medical and Health Sciences, Tel Aviv University; Rabin Medical Center

PD is known to be associated with brain inflammation, microglia activation and secretory neurotoxic activities, including reactive oxygen species (ROS), which lead to oxidative stress and neurodegeneration. Catalase is one of the most potent antioxidants in nature, albeit the BBB severely limits transport of this large protein. Previous publications have shown that monocytes and macrophages EVs loaded with catalase19, or HEK-293T engineered EVs loaded with catalase mRNA20 were detected in PD mouse brain following administration and provide significant neuroprotective effects. 
We propose a new treatment for PD based on MSC-Evs loaded with catalase. We will study the possible synergistic effect of EVs and catalase in a mouse model of PD (6-OHDA). Explore >>

Personalized Cannabis Therapy Based on Objective Measurements to Reduce Adverse Reactions in Parkinson’s Disease Patients

• Prof. Mordechai Lorberboym | Emeritus, School of Continuing Medical Education, Gray Faculty of Medical and Health Sciences, Tel Aviv University
   
• Prof. Yankel Gabet | Department of Anatomy and Anthropology Gray Faculty of Medical and Health Sciences , Tel Aviv University

Artificial intelligence image analysis of  biophotonic images allows correlations with multiple pathophysiological states, including stress and vitality (the average electrical potential of the sodium potassium pump. Bio-Well is used to map and analyze various groups of parameters (i.e. anxiety, energy, right-left symmetry and organ balance),32 and to quantitatively assess effects of treatment on various spine symptoms;33 Such effects are relevant to CNNCP patients, and may further elucidate changes during MCT in PD patients, as a complementary tool to fNIRS and EEG. Moreover, a personalized treatment approach should assess not only cannabinoids’ values, but also possible effects of terpene-modulation of MCT. We hypothesize that fNIRS, EEG, and Bio-Well measurements, supported by olfactometer measurements may provide new unbiased data that will enable the optimal use of MCT in PD patients.
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Bio-Engineering Functional, Implantable Human Dopaminergic Networks to Treat Parkinson’s Disease

• Prof. Tal Dvir | Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences; Faculty of Engineering, Department of Biomedical Engineering, Tel Aviv University 

We have previously developed omentum-derived hydrogel matrices that can provide such supportive environments, showing that they are biocompatible, support cell attachment, interactions, proliferation, and differentiation11,25,26. We further demonstrated the production of various cellular implants (including dopaminergic) using the omentum hydrogel, while conceptually both the cells and the scaffold are derived from the patient, therefore eliciting reduced immune response 11,25,27. Based on this technology we have recently engineered motor neuron implants25, which are now on the path to clinical trials in paralyzed patients (matricelf.com). Using the same approach, we suggest engineering dopaminergic, injectable tissue grafts by differentiating human iPSCs into DNs within the omentum hydrogel (Fig.1). The ultimate goal of this proposal is to create functional dopaminergic implants for treating PD.
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• Prof. Uri Ashery | George S. Wise Faculty of Life Sciences, Department of Neurobiology, Tel Aviv University
   
• Prof. Ben Maoz | Faculty of Engineering, Department of Biomedical Engineering, Tel Aviv University
   
• Prof. Roded Sharan | Blavatnik  School of Computer Science and AI, Raymond & Beverly Sackler Faculty of Exact Sciences

In this multidisciplinary approach, our ultimate goal is to develop a human-relevant in vitro platform for studying Parkinson's disease (PD), and to use it for identifying PD-associated abnormal pathways using patient-specific differentiated neurovascular niche. To achieve this ambitious goal, we will pursue the following aims (Figure 1): a) Establish a patient-based human iPSC-derived BBB and neurons (NVU) with LRRK2 and GBA-1 genes mutations as well as dual LRRK2/GBA-1 mutations. b) Identifying the canonical pathways and functional changes caused by the dual mutation by performing systematic measurements of gene expression levels and functional response under common PD mutations. c) Derive predictive models of cellular response to mutations allowing manipulating specific pathways. The research team consists of an expert in NVU-on-a-Chip and biosensors (Ben Maoz, Bioengineering), an expert in neuroscience and cellular and molecular aspects of Parkinson’s disease (Uri Ashery, Neurobiology) and an expert in computational modeling (Roded Sharan, Computer Science). The outcome of our integrated ECB framework will be: (i) novel human personalized platform for drug and disease assessment, and (ii) newly identified genomic variations, cellular PD associated phenotypes and disease pathways that can be used to develop novel and specific therapeutic strategies. Explore >>